Adolescence is a critical neurodevelopmental period associated with dramatic increases in rates of substance use (SU). Identifying the pathways to SU and its effects on child and adolescent development is critically important, as the effects of substance use during ongoing maturation likely have long-lasting effects on brain function and behavioral, health, and psychological outcomes. This Research Project Site application from the University of Southern California/Children's Hospital Los Angeles and UCLA is in response to RFA-DA-15-015 as part of the ABCD-USA Consortium (8/13), to prospectively determine the neurodevelopmental and behavioral predictors and consequences of SU on children and adolescents. A representative community sample of 850 9-10 year olds enriched for high-risk characteristics will be recruited, contributing to the sample of 11,111 to be collected from 11 hubs across the ABCD-USA Consortium. All participants will undergo a comprehensive baseline assessment, including state-of-the-art brain imaging, comprehensive neuropsychological testing, bioassays, mobile monitoring and careful assessment of SU, environment, psychopathological symptoms, and social functioning every 2 years. Interim annual interviews and quarterly web-based assessments will provide refined temporal resolution of behaviors, development, and life events with minimal participant burden. These Consortium-wide data obtained during the course of this project will elucidate: 1) the effects of SU patterns on the adolescent brain; 2) the effects of SU on behavioral and health outcomes; 3) the bidirectional relationship between psychopathology and SU patterns; 4) the effects of individual genetic, behavioral, neurobiological, and environmental differences on risk profiles and SU outcomes; and 5) the gateway interactions between use of different substances. Elements Unique to This Site: Our Research Project focuses on the mediating or moderating effects of 1) pubertal hormones and sex differences, 2) socioeconomic (SES) factors, and 3) prenatal exposure (PE) to drugs of abuse on SU and other psychopathologies. These three factors are known to influence timing and trajectories of neurodevelopment, and have been linked to SU, but are seldom studied in tandem in neurodevelopmental studies of typically developing children. In this proposal, in conjunction with the larger ABCD-USA consortium, we are in a unique position to investigate the extent that SES and PE individually or interactively perturb the timing or outcomes of maturation of frontolimbic circuits important in reward processing and decision making, and, how pubertal changes (independent of age) may correspond with the onset of SU and co-occurring psychopathology within the context of the developmental environment. In Y03, we will focus on studying cross-sectional relationships between brain structure and function and puberty, SES and PE prior to onset of SU, and in subsequent years, we will focus on longitudinal studies from onset of SU and SU disorder progression, and precursors or consequences of SU on brain structure and function in Y6-Y10.